Ketamine ((2-(2-chlorophenyl)-2-(methylamino)-cyclohexanone) is a general anesthetic used by anesthesiologists, veterinarians, and researchers. Nasal administration of ketamine, in one instance with midazolam, to achieve sedation for an ophthalmic procedure, and prior to elective surgery in healthy children has been reported (Louon et al., 1993, Br. J. Ophthalmol. 77: 529-530; Weksler et al., 1993, Can. J. Anaesthesia 40: 119-121). Usually, ketamine is administered intramuscularly (i.m.) or intravenously (i.v.) for induction of anesthesia.
Ketamine has also been known to have analgesic properties (Domino et al., 1965, Clin. Pharmacol. Ther. 6: 279); analgesia can be achieved with subanesthetic doses of ketamine (Bovill, 1971, Br. J. Anaesth. 43: 496; Sadove et al., 1971, Anesth. Analg. 50: 452-457). The drug is administered by various routes, including i.v., i.m., caudal, intrathecal, and subcutaneous (s.c.). Subcutaneous administration of ketamine has been used to treat pain following surgery and associated with terminal cancer (see, e.g., Oshima et al., 1990, Can. J. Anaesth. 37: 385-386). Ketamine hydrochloride administered via a subcutaneous cannula was reported to successfully treat phantom limb pain (Stannard and Porter, 1993, Pain 54: 227-230).
Detoxification and treatment of addictive diseases generally involves a complex and poorly understood interplay between the psychological and physiological components. Seven withdrawal symptoms can accompany detoxification from substances such as alcohol, narcotics, depressants, and stimulants. While marked by significantly less severe physical symptoms, the withdrawal symptoms associated with detoxification from smoking may include nervousness, shakiness, difficulty concentrating, impatience, and ill tempered behavior. Furthermore, detoxification is only an acute component of the treatment of addictive disease. Long term treatment, to be successful, must provide strong physical and psychological reinforcements to avoid the addition.
Thus, an area of grave concern for medicine is detoxification and withdrawal from dependence on addictive substances, including narcotics, cocaine, alcohol, and tobacco (both nicotine and smoking itself). In particular, medicine provides no satisfactory relief for withdrawal from smoking or from nicotine addiction. While the general perception holds that addiction to tobacco is the least profound of these addictions, from a public health perspective, it may be the most important. Furthermore, the current supports for treatment of smoking or nicotine addiction, such as the nicotine transdermal patch or nicotine gum, treat the addiction with an addictive substance delivered by tobacco use. Such treatment is logically impossible: it reinforces the very behavior to be eliminated. No adequate substitute, capable of reinforcing the absence of tobacco ingestion, is presently available.
Thus, there is still a critical need in the art for an agent that can assist in detoxification and withdrawal from addiction to substances, particularly smoking.
The citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention.